36212-73-4Relevant academic research and scientific papers
Reactivity and mechanism of α-nucleophile scaffolds as catalytic organophosphate scavengers
Wong, Pamela T.,Bhattacharjee, Somnath,Cannon, Jayme,Tang, Shengzhuang,Yang, Kelly,Bowden, Sierra,Varnau, Victoria,O'Konek, Jessica J.,Choi, Seok Ki
supporting information, p. 3951 - 3963 (2019/04/30)
Despite their unique benefits imparted by their structure and reactivity, certain α-nucleophile molecules remain underexplored as chemical inactivators for the topical decontamination of reactive organophosphates (OPs). Here, we present a library of thirty α-nucleophile scaffolds, each designed with either a pyridinium aldoxime (PAM) or hydroxamic acid (HA) α-nucleophile core tethered to a polar or charged scaffold for optimized physicochemical properties and reactivity. These library compounds were screened for their abilities to catalyze the hydrolysis of a model OP, paraoxon (POX), in kinetic assays. These screening experiments led to the identification of multiple lead compounds with the ability to inactivate POX two- to four-times more rapidly than Dekon 139 - the active ingredient currently used for skin decontamination of OPs. Our mechanistic studies, performed under variable pH and temperature conditions suggested that the differences in the reactivity and activation energy of these compounds are fundamentally attributable to the core nucleophilicity and pKa. Following their screening and mechanistic studies, select lead compounds were further evaluated and demonstrated greater efficacy than Dekon 139 in the topical decontamination of POX in an ex vivo porcine skin model. In addition to OP reactivity, several compounds in the PAM class displayed a dual mode of activity, as they retained the ability to reactivate POX-inhibited acetylcholine esterase (AChE). In summary, this report describes a rationale for the hydrophilic scaffold design of α-nucleophiles, and it offers advanced insights into their chemical reactivity, mechanism, and practical utility as OP decontaminants.
Nonenzymatic Catalysis by Metal Ions and Phosporic Acid Esters of Hydroxamic Acid Formation
Saygin, Oemer,Decker, Peter
, p. 727 - 730 (2007/10/02)
Nonenzymatic Catalysis by bivalent ions of Be, Mg, Ca, Zn, Mn, Ni and Co and bioorganic phosphates of the formation of hydroxamic acids from acetate or amino acids has been studied systematically.Increased yields of hydroxamate were observed at particular combinations of reactants.The most prominent increase (ca. 15-fold) was found with acetate and Ni++, and with a combination of ATP and Be++.Among others especially ribose-5-phosphate and glucose-5-phosphate enhanced yields in the presence of most metal ions.Since no release of inorganic phosphate was observed, this effect cannot be interpreted as an evidence for intermediate transphosphorylation reactions; it may also result from simple catalytic effects of metal sugar complexes. - Keywords: Prebiological Evolution, Bioids, Transphosphorylation, Hydroxylamine, Acylate Activation
